Methods of correcting vision

ABSTRACT

Methods of lenticule extraction to correct for presbyopia that account for epithelial remodeling.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation-in-part of U.S. application Ser. No.14/217,056, filed Mar. 17, 2014, which is a continuation-in-part of U.S.application Ser. No. 12/418,325, filed Apr. 3, 2009, now U.S. Pat. No.8,900,296. U.S. application Ser. No. 12/418,325 claims the priority ofU.S. Prov. No. 61/042,659, filed Apr. 4, 2008 and U.S. Prov. No.61/155,433 filed Feb. 25, 2009.

All of the aforementioned applications are incorporated by referenceherein.

The following applications and publications are also incorporated byreference herein: U.S. Pat. No. 8,057,541, issued Nov. 15, 2011; U.S.Pub. No. 2011/0218623, published Sep. 8, 2011; and U.S. Pub. No.2008/0262610, published Oct. 23, 2008.

INCORPORATION BY REFERENCE

All publications and patent applications mentioned in this specificationare herein incorporated by reference to the same extent as if eachindividual publication or patent application was specifically andindividually indicated to be incorporated by reference.

BACKGROUND

Abnormalities in the human eye can lead to vision impairment such asmyopia (near-sightedness), hyperopia (farsightedness), astigmatism, andpresbyopia. A variety of devices and procedures have been developed toattempt to address these abnormalities.

One type of device that has been proposed is a corneal implant, such asan onlay, which is placed on top of the cornea such that the outer layerof the cornea (i.e., the epithelium), can grow over and encompass theonlay. An inlay is a corneal implant that is surgically implanted withinthe cornea beneath a portion of corneal tissue by, for example, cuttinga flap in the cornea and positioning the inlay beneath the flap. Aninlay can also be positioned within a pocket formed in the cornea.

Inlays can alter the refractive power of the cornea by changing theshape of the anterior surface of the cornea, by creating an opticalinterface between the cornea and an implant by having an index ofrefraction different than that of the cornea (i.e., has intrinsicpower), or both. The cornea is the strongest refracting optical elementin the eye, and altering the shape of the anterior surface of the corneacan therefore be a particularly useful method for correcting visionimpairments caused by refractive errors.

LASIK (laser-assisted in situ keratomileusis) is a type of refractivelaser eye surgery in which a laser is used to remodel a portion of thecornea after lifting a previous cut corneal flap.

Presbyopia is generally characterized by a decrease in the eye's abilityto increase its power to focus on nearby objects due to, for example, aloss of elasticity in the crystalline lens that occurs over time.Ophthalmic devices and/or procedures (e.g., contact lenses, intraocularlenses, LASIK, inlays) can be used to address presbyopia using threecommon approaches. With a monovision prescription, the diopter power ofone eye is adjusted to focus distant objects and the power of the secondeye is adjusted to focus near objects. The appropriate eye is used toclearly view the object of interest. In the next two approaches,multifocal or bifocal optics are used to simultaneously, in one eye,provide powers to focus both distant and near objects. One commonmultifocal design includes a central zone of higher diopter power tofocus near objects, surrounded by a peripheral zone of the desired lowerpower to focus distant objects. In a modified monovision prescription,the diopter power of one eye is adjusted to focus distance objects, andin the second eye a multifocal optical design is induced by theintracorneal inlay. The subject therefore has the necessary diopterpower from both eyes to view distant objects, while the near power zoneof the multifocal eye provides the necessary power for viewing nearobjects. In a bilateral multifocal prescription, the multifocal opticaldesign is induced in both eyes. Both eyes therefore contribute to bothdistance and near vision.

Regardless of the vision correction procedure and/or devices implanted,it is important to understand the cornea's natural response to theprocedure to understand how the cornea will attempt to reduce orminimize the impact of the vision correction procedure.

Specific to understanding a response to an inlay, Watsky et al. proposeda simple biomechanical response in Investigative Ophthalmology andVisual Science, vol. 26, pp. 240-243 (1985). In this biomechanical model(“Watsky model”), the anterior corneal surface radius of curvature isassumed to be equal to the thickness of the lamellar corneal material(i.e., flap) between the anterior corneal surface and the anteriorsurface of a corneal inlay plus the radius of curvature of the anteriorsurface of the inlay.

Reviews of clinical outcomes for implanted inlays or methods for designgenerally discuss relatively thick inlays (e.g., greater than 200microns thick) for which the above simple biomechanical response modelhas some validity. This is because the physical size of the inlaydominates the biomechanical response of the cornea and dictates theprimary anterior surface change. When an inlay is relatively small andthin, however, the material properties of the cornea contributesignificantly to the resulting change in the anterior corneal surface.Petroll et al. reported that implantation of inlays induced a thinningof the central corneal epithelium overlying the inlay. “Confocalassessment of the corneal response to intracorneal lens insertion andlaser in situ keratomileusis with flap creation using IntraLase,” J.Cataract Refract. Surg., vol. 32, pp 1119-1128 (July 2006).

Huang et al. reported central epithelial thickening after myopicablation procedures and peripheral epithelial thickening and centralepithelial thinning after hyperopic ablation procedures. “MathematicalModel of Corneal Surface Smoothing After Laser Refractive Surgery,”America Journal of Ophthalmology, March 2003, pp 267-278. The theory inHuang does not address correcting for presbyopia, nor does it accuratelypredict changes to the anterior surface which create a center nearportion of the cornea for near vision while allowing distance vision inan area of the cornea peripheral to the center near portion.Additionally, Huang reports on removing cornea tissue by ablation asopposed to adding material to the cornea, such as an intracorneal inlay.

What is needed is an understanding of the cornea's response to thecorrection of presbyopia. An understanding of the corneal responseallows the response to be compensated for when performing the procedureon the cornea and/or implanting an implant within the cornea, either ofwhich can be used to alter the curvature of the cornea. A need alsoexists for understanding the cornea's response to a vision correctionprocedure that creates a center zone for near vision while providingdistance vision in a region peripheral to the central zone.

SUMMARY OF THE DISCLOSURE

One aspect of the disclosure is a method of correcting vision forpresbyopia, comprising: remodeling the stroma with a laser to create anintracorneal shape, wherein the corneal shape includes a central regionwith a thickness that is about 50 microns or less measured from anextension of a shape of a peripheral region of the corneal shape,wherein remodeling a portion of the stroma increases a curvature of acentral portion of the anterior surface of the cornea with a centralelevation change for near vision while allowing distance vision in aregion peripheral to the central portion; wherein the corneal shapecompensates for epithelial remodeling of the epithelial layer of thecornea in response to remodeling the stroma, and wherein the centralregion with a thickness that is about 50 microns or less measured froman extension of a shape of the peripheral region of the corneal ablationshape is 3 to 7 times the central elevation change.

In some embodiments the remodeling step is performed without ablatingthe stroma.

In some embodiments the remodeling step creates a corneal lenticule, andthe intracorneal shape is defined by a posterior lenticule incision.

One aspect of the disclosure is a method of correcting vision forpresbyopia, comprising: creating a lenticule in a stroma, whereincreating the lenticule includes creating an anterior lenticule incisionand a posterior lenticule incision with a femtosecond laser, wherein oneof the posterior lenticule incision and the anterior lenticule incisionhas a central region and a peripheral region, the central region havingincreased curvature relative to the peripheral region, and a centralthickness that is about 50 microns or less measured from an extension ofthe peripheral region, the central region having an outer diameterbetween 1 mm and 4 mm; and removing the lenticule from the stroma,wherein removing the lenticule increases the curvature of a centralportion of the anterior surface of the cornea with a central elevationchange for near vision; wherein one of the posterior lenticule incisionand anterior lenticule incision compensates for epithelial remodeling ofthe epithelial layer of the cornea in response to cutting and removingthe lenticule in the stroma, and wherein the central thickness that isabout 50 microns or less measured from an extension of the peripheralregion is 3 to 7 times the central elevation change.

In some embodiments creating the anterior lenticule incision comprisescreating the anterior lenticule incision between 5 microns and 250microns deep in the stroma.

In some embodiments removing the lenticule comprises creating a cornealflap.

In some embodiments the method of correcting vision does not includecreating a corneal flap.

One aspect of the disclosure is a method of correcting vision forpresbyopia, comprising: creating a lenticule in a stroma, whereincreating the lenticule includes creating an anterior lenticule incisionand a posterior lenticule incision with a femtosecond laser, wherein theposterior lenticule incision has a posterior peripheral region and aposterior central region, and the anterior lenticule incision has ananterior central region and an anterior peripheral region, the anteriorand posterior central regions having increased curvature relative to theanterior and posterior peripheral regions, the anterior and posteriorcentral regions having a combined thickness that is about 50 microns orless measured from extension of the peripheral regions, the anterior andposterior central regions having an outer diameter between 1 mm and 4mm; and removing the lenticule from the stroma, wherein removing thelenticule increases the curvature of a central portion of the anteriorsurface of the cornea with a central elevation change for near vision;wherein the posterior lenticule incision and the anterior lenticuleincision compensate for epithelial remodeling of the epithelial layer ofthe cornea in response to cutting and removing the lenticule in thestroma, and wherein the combined central thickness that is about 50microns or less measured from extensions of the peripheral regions is 3to 7 times the central elevation change.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows an exemplary intracorneal inlay which can be implantedwithin cornea tissue according to methods herein.

FIGS. 2 and 3 show an exemplary steepening of a central portion of theanterior surface of the cornea after an inlay has been implanted withinthe cornea.

FIG. 4 illustrates how an inlay as described herein can be implantedwithin a cornea to provide center near vision and peripheral distancevision in an eye.

FIG. 5 illustrates the locations of epithelial thinning and thickeningafter an inlay has been implanted within a cornea.

FIG. 6 illustrates the shape change of Bowman's layer and the anteriorsurface of the cornea in response to an inlay being implanted within thecornea.

FIGS. 7 and 9 present clinical data (e.g., distance and near visualacuity and the refractive effect created by the inlay) and the change inanterior corneal surface elevation derived from pre-op and post-opwavefront measurements of patients in which an inlay was implanted.

FIGS. 8 and 10 chart the changes in elevation of the anterior surface ofthe cornea (i.e., the difference in elevation between pre-op andpost-op) versus the radius of the anterior surface of the cornea forpatients in which an inlay was implanted.

FIGS. 11-13 illustrate an exemplary method of lenticule extraction thatcorrects for presbyopia and accounts for epithelial remodeling.

DETAILED DESCRIPTION

This disclosure relates to methods of vision correction and methods ofcompensating for a cornea's response to the vision correction procedureto invoke a desired corneal shape change. The disclosure includesmethods of correcting presbyopia. In some embodiments the methodsinclude implanting a corneal inlay within cornea tissue to correct forpresbyopia while compensating for the inlay's presence within thecornea. The disclosure also provides methods of increasing the curvatureof a central portion of the anterior surface of the cornea to providenear vision in the central portion while providing distance visionperipheral to the central portion. In some particular embodiments aninlay is implanted in the cornea to cause the central portion toincrease in curvature to provide near vision.

The cornea can be generally considered to be comprised of, from theanterior A to posterior P direction, the epithelium, Bowman's layer,stroma, Descemet's membrane, and the endothelium. The epithelium is alayer of cells that can be thought of as covering the surface of thecornea and it is only about five (5) cells thick with a thickness ofabout 50 microns. The stroma is the thickest layer of the cornea andgives the cornea much of its strength, and most refractive surgeriesinvolve manipulating stroma cells. Descemet's membrane and theendothelium are considered the posterior portion of the cornea and aregenerally not discussed herein. The instant disclosure focuses thediscussion on the epithelium, Bowman's layer, and the stroma.

As disclosed herein a cornea's response to a vision correction procedureis generally described as a “physiological response,” or variationsthereof. The physiological response may include any biomechanicalresponse, which is the corneal response due to an interaction withand/or alteration to Bowman's layer. A physiological response as usedherein may also include an epithelial response, which includes a naturalremodeling of the epithelial layer in response to a vision correctionprocedure.

In some embodiments a corneal inlay is used to correct for presbyopia.FIG. 1 is a side cross-sectional view of an exemplary corneal inlay 10with diameter D, central thickness T along the central axis CA of theinlay, anterior surface 12, posterior surface 18, outer edge 16, andoptional beveled portion 14. Anterior surface 12 has an anterior radiusof curvature, and posterior surface 18 has a posterior radius ofcurvature. Outer edge 16 connects posterior surface 18 and beveledportion 14. The beveled portion may be considered a part of the anteriorsurface or may be considered a separate surface between the anteriorsurface and the posterior surface. Exemplary inlay 10 can be used totreat, for example without limitation, presbyopia.

Inlay 10 can have any features or parameters described herein or in anyof the following patent applications and patents: U.S. patentapplication Ser. No. 11/738,349, filed Apr. 20, 2007, (U.S. PatentApplication No. US 2008/0262610 A1), U.S. patent application Ser. No.11/381,056, filed May 1, 2006 (Patent Application Pub. US 2007/0255401A1), U.S. patent application Ser. No. 11/554,544, filed Oct. 30, 2006(Patent Application Pub. US 2007/0203577 A1), U.S. patent applicationSer. No. 11/293,644, filed Dec. 1, 2005 (Patent Application Pub. US2007/0129797 A1), U.S. patent application Ser. No. 11/421,597, filedJun. 1, 2006 (Patent Application Pub. US 2007/0280994 A1), Ser. No.10/924,152, filed Aug. 23, 2004 (Patent Application Pub. US 2005/0178394A1), U.S. patent application Ser. No. 11/106,983, filed Apr. 15, 2005(Patent Application Pub. US 2005/0246016 A1), U.S. patent applicationSer. No. 10/837,402, filed Apr. 30, 2004 (Patent Application Pub. US2005/0246015 A1), U.S. patent application Ser. No. 10/053,178, filedNov. 7, 2001 (U.S. Pat. No. 6,623,522), U.S. patent application Ser. No.10/043,975, filed Oct. 19, 2001 (U.S. Pat. No. 6,626,941), U.S. patentapplication Ser. No. 09/385,103, filed Aug. 27, 1999 (U.S. Pat. No.6,361,560), and U.S. patent application Ser. No. 09/219,594, filed Dec.23, 1998 (U.S. Pat. No. 6,102,946), all of which are incorporated byreference herein.

Inlay 10 can be implanted within the cornea by known procedures such asby cutting a flap 25 (see FIG. 2) in the cornea, lifting the flap 25 toexpose the corneal bed, placing the inlay 10 on the exposed cornea bed,and repositioning the flap 25 over the inlay 10. When flap 25 is cut, asmall section of corneal tissue is left intact, creating a hinge forflap 25 so that flap 25 can be repositioned accurately over the inlay20. After the flap 25 is repositioned over the inlay, the flap adheresto the corneal bed. In some embodiments in which an inlay is positionedbeneath a flap, the inlay is implanted between about 100 microns andabout 200 microns deep in the cornea. In some embodiments the inlay ispositioned at a depth of between about 130 microns to about 160 microns.In some particular embodiments the inlay is implanted at a depth about150 microns.

The inlay can also be implanted by creating a pocket in the cornea andpositioning the inlay within the formed pocket. Pockets are generallycreated deeper in the cornea than flaps, which can help in preventingnerve damage. In some embodiments in which a pocket is formed, the inlayis implanted at a depth of between about 150 microns and about 300microns. In some embodiments the inlay is positioned at a depth ofbetween about 200 microns to about 250 microns.

The inlay should be positioned on the corneal bed with the inlaycentered on the subject's pupil or visual axis. Inlay 10 can beimplanted in the cornea at a depth of about 50% or less of the corneathickness measured from the anterior surface of the cornea(approximately 250 μm or less). The flap 25 may be cut using, forexample, a laser (e.g., a femtosecond laser) or a mechanical keratome.Additional methods or details of implanting the inlay can be found in,for example, U.S. patent application Ser. No. 11/293,644, filed Dec. 1,2005 (Patent Application Pub. US 2007/0129797 A1) and U.S. patentapplication Ser. No. 11/421,597, filed Jun. 1, 2006 (Patent ApplicationPub. US 2007/0280994 A1), which are incorporated by reference herein.

As can be seen in FIG. 2, inlay 10, once implanted within the cornea,changes the refractive power of the cornea by altering the shape of theanterior surface of the cornea from pre-operative shape 35 (shown withdashed line) to post-operative shape 40 (shown as a solid line). In FIG.2, the inlay changes the shape of a central portion of the anteriorsurface of the cornea, while a peripheral portion of the anteriorsurface peripheral to the central portion does not change shape. FIG. 2shows an elevation change in the central portion of the anterior surfaceof the cornea. The elevation change includes a steepening of the centralportion. The curvature of the central zone is increased to provide fornear vision in the central portion, while the shape of the peripheralzone does not change and provides for distance vision peripheral to thecentral zone. The inlay in FIG. 2 can be used to correct for presbyopiabecause the central zone's increased curvature increases the eye'sability to focus on near objects.

In some embodiments the inlay has properties similar to those of thecornea (e.g., index of refraction around 1.376, water content of 78%,etc.), and may be made of hydrogel or other clear bio-compatiblematerial. The inlay can be comprised of a variety of materialsincluding, for example and without limitation, Lidofilcon A, Poly-HEMA(hydroxyethyl methylacrylate), poly sulfone, silicone hydrogel. In someembodiments the inlay comprises from about 20% to about 50% HEMA(hydroxyethyl methylacrylate), from about 30% to about 85% NVP (N-vinylpyrrolidone), and/or about 0% to about 25% PVP (polyvinyl pyrrolidone).Other formulations of such materials cover compositions ranging fromabout 15% to about 50% MMA (methyl methylacrylate), from about 30% toabout 85% NVP, and/or about 0% to about 25% PVP (polyvinyl pyrrolidone).

In some embodiments the water content of these compositions ranges fromabout 65% to about 80%. In one particular embodiment the inlay comprisesabout 78% NVP and about 22% MMA(methyl methacrylate), allymethacrylateas a crosslinker, and AIBN (azobisisobutylonitrile) as the initiator.Exemplary additional details and examples of the inlay material can befound in U.S. patent application Ser. No. 11/738,349, filed Apr. 20,2007, (U.S. Patent Application No. US 2008/0262610 A1), which isincorporated by reference herein. In some embodiments the inlay has anindex of refraction of approximately 1.376+/−0.0.008, which issubstantially the same as the cornea. As a result, the inlay does nothave intrinsic diopter power. The inlay can, however, have an index ofrefractive that is substantially different than the index of refractionof the cornea such that the inlay has intrinsic diopter power (inaddition to changing the curvature of the anterior surface of thecornea). Exemplary details of a lens with intrinsic diopter power andmethods of use, the features of which can be incorporated into themethods herein, are described in U.S. patent application Ser. No.11/381,056, filed May 1, 2006 (Patent Application Pub. US 2007/0255401A1), which is incorporated herein by reference.

FIG. 3 illustrates a cross-sectional side view of an exemplarybiomechanical effect of inlay 210 on the shape of the post-operativeanterior corneal surface 240. Inlay 210 has center thickness 265, edgethickness 250, anterior surface 215, and posterior surface 220. The“effect” zone (which may also be referred to herein as “central zone”),or the region of the anterior surface whose curvature is altered due tothe presence of the inlay, extends peripherally beyond the diameter ofinlay 210. The “effect” zone comprises the geometric projection of theinlay diameter on the anterior surface 260 and “an outer effect zone”255 peripheral to the projection of the inlay diameter. The effect zonehas a center thickness 275.

FIG. 4 illustrates an exemplary embodiment in which an inlay is used toprovide near vision while providing distance vision to correct forpresbyopia. The eye comprises cornea 110, pupil 115, crystalline lens120, and retina 125. In FIG. 4, implanting the inlay (not shown)centrally in the cornea creates a small diameter “effect” zone 130 inthe cornea. Both the inlay diameter and effect zone diameter are smallerthan the pupil 115 diameter. The “effect” zone 130 provides near visionby increasing the curvature of the anterior corneal surface in a centralregion of the cornea, and therefore the diopter power of the “effect”zone 130. The region of the cornea peripheral to the “effect” zone 135has a diameter less than the diameter of the pupil and provides distancevision. The subject's near vision is therefore improved while minimizingthe loss of distance vision in the treated eye.

An exemplary advantage of this type of inlay is that when concentratingon nearby objects 140, the pupil naturally becomes smaller (e.g., nearpoint miosis) making the inlay effect even more effective. Near visioncan be further increased by increasing the illumination of a nearbyobject (e.g., turning up a reading light). Because the “effect” zone 130is smaller than the diameter of pupil 115, light rays 150 from distantobject(s) 145 by-pass the inlay and refract using the region of thecornea peripheral to the “effect” zone to create an image of the distantobjects on the retina 125. This is particularly true with larger pupils.At night, when distance vision is most important, the pupil naturallybecomes larger, thereby reducing the inlay effect and maximizingdistance vision.

A subject's natural distance vision is in focus only if the subject isemmetropic (i.e., does not require correction for distance vision). Manysubjects are ammetropic, requiring either myopic or hyperopic refractivecorrection. Especially for myopes, distance vision correction can beprovided by myopic Laser in Situ Keratomileusis (LASIK) or other similarcorneal refractive procedures. After the distance corrective procedureis completed, the small inlay can be implanted in the cornea to providenear vision. Since LASIK requires the creation of a flap, the inlay maybe inserted concurrently with the LASIK procedure. The inlay may also beinserted into the cornea after the LASIK procedure as the flap can bere-opened. This type of inlay may therefore be used in conjunction withother refractive procedures, such as LASIK for correcting myopia orhyperopia.

In some embodiments (e.g., as shown in FIG. 4) an inlay is implanted tocreate an effect zone that is less than the pupil diameter and is usedfor correcting presbyopia. Presbyopia is generally characterized by adecrease in the ability of the eye to increase its power to focus onnearby objects due to, for example, a loss of elasticity in thecrystalline lens over time. Typically, a person suffering fromPresbyopia requires reading glasses to provide near vision. For earlypresbyopes (e.g., about 45 to 55 years of age), at least 1 diopter istypically required for near vision. For complete presbyopes (e.g., about60 years of age or older), between 2 and 3 diopters of additional poweris required. In an exemplary embodiment, a small inlay (e.g., about 1 toabout 3 mm in diameter) is implanted centrally in the cornea to inducean “effect” zone on the anterior corneal surface (e.g., about 2 to about4 mm in diameter) that is smaller than the optical zone of the corneafor providing near vision while also allowing distance vision in aregion of the cornea peripheral to the effect zone.

The first step in correcting the vision of a subject by altering thecornea is generally determining the desired post-operative shape of theanterior corneal surface which will provide the desired refractive powerchange (i.e., determining the shape change for the anterior surface ofthe cornea). The shape of the desired anterior surface may be the resultof a biomechanical response as well as epithelial remodeling of theanterior corneal surface as a result of the vision correction procedure.Corneal epithelial remodeling will be described in more detail below.Based on a biomechanical response and an epithelial response, the visioncorrection procedure is performed (e.g., implanting an inlay) to inducethe desired anterior surface change.

This disclosure includes an exemplary method of determining a desiredanterior corneal shape to provide for corrective vision. One particularembodiment in which the method includes implanting an inlay within thecornea to provide for center near and peripheral distance will bedescribed. In some embodiments a central zone on the anterior cornealsurface with a sharp transition is preferred (i.e., substantiallywithout an outer effect zone which can be seen in FIG. 3). A sharptransition maximizes both the near and distance power efficiencies. Inpractice, the effects of epithelial remodeling typically prevent “sharp”transitions. Empirically, the anterior surface change induced by theinlay can be given by a symmetric polynomial of at least eighth order:

Elev(r)=a0+a2×r ² +a4×r ⁴ +a6×r ⁶ +a8×r ⁸  Eq 1.

Where “Elev” is the change in anterior corneal surface elevation due tothe inlay, a0, a2, a4, a6 and a8 are the coefficients governing theshape And “r” is the radial extent location from the center of theanterior surface change.

The elevation change discussed herein is azimuthally symmetric in planeperpendicular to the axis of the cornea. But orthogonal asymmetries maybe included with more complex inlay designs, attempting to correction ofcorneal astigmatism, pre-existing in the subject's eye. Physically,there are useful restrictions on the form of the elevation expression.At r=0, the elevation change is maximal and is central height “hctr”.From the symmetry, at r=0, the first derivative of elevation expressionmust be zero. The extent of the inlay-induced change is limited to amaximal radius (r_(z)), where Elev(r_(z))=0. And because the elevationsmoothly transitions to the original cornea at r_(z), the firstderivative may also be zero; i.e., dElev(r_(z))/dr=0.

With these restrictions, the elevation change can be characterized byfour independent parameters: hctr, r_(z), a6 and a8. And the remainingcoefficients are given by:

a0=hctr

a2=2*alpha/rẑ2−beta/2/rz

a4=beta/2/rẑ3−alpha/rẑ4

Where:

-   -   alpha=−hctr−a6*rẑ6−a8*rẑ8    -   beta=−6*a6*rẑ5−8*a8*rẑ7

Thus, the ideal anterior corneal elevation change can be expressed byfour independent parameters: hctr, r_(z), a6 and a8.

Table 1 provides ideal anterior corneal surface changes for threespectacle ADD powers (1.5 diopters, 2.0 diopters, and 2.5 diopters) andfor three pupil sizes (small, nominal and large) when using near vision.

TABLE 1 Examples of Ideal Anterior Corneal Surface Change Designs Designrad Type Pupil ADD “hctr” zone a6 a8 (mm) Size (diopters) (microns) (mm)(mm⁻⁵) (mm⁻⁷) MaxN small 1.5 4.30 1.39 −4.500E−04 2.800E−04 @ 2.5 MaxNnominal 1.5 5.06 1.50 −2.830E−04 1.466E−04 @ 3.0 MaxN large 1.5 6.241.66 −3.374E−04 9.972E−05 @ 3.5 MaxN small 2.0 5.38 1.36 −2.450E−038.100E−04 @ 2.5 MaxN nominal 2.0 7.15 1.55 −1.830E−03 4.420E−04 @ 3.0MaxN large 2.0 10.70 1.87 −6.014E−04 1.108E−04 @ 3.5 MaxN small 2.5 6.581.38 −2.247E−03 7.904E−04 @ 2.5 MaxN nominal 2.5 9.87 1.68 −7.639E−041.950E−04 @ 3.0 MaxN large 2.5 13.70 1.97 −3.658E−04 7.109E−05 @ 3.5

Performing the optical ray-trace optimization to derive the optimalanterior corneal elevation change (Elev) requires a model eye whichmimics the key optical functions of the human eye. The finite eye modelby Navarro (Accommodation dependent model of the human eye withaspherics, R. Navarro. et al., JOSA Vol 2 No 8 1985 p. 1273-1281)provides one such model. For these design purposes, the Navarro providesanatomically correct values for the corneal physical and opticalproperties and provides total eye properties such as normal values forthe total eye spherical aberrations, chromatic aberration andStiles-Crawford effect. Other model eyes can be also used if theyspecify these criteria.

To include the anterior corneal elevation change (Elev) in the Navarroeye model, the Elev surface is added to the anterior surface of theNavarro eye model. Calculations of the image quality created by theanterior surface change to the eye model are accomplished using any ofmany commercial ray-trace software packages. For the examples provided,the Zemax-EE Optical Design Program (2008) from the Zemax DevelopmentCorporation was used.

The objective of the ray-trace optimization is to find the elevationsurface parameters (hctr, r_(z), a6 and a8) that maximize the opticalperformance for a given set of assumptions. There are many opticalmetrics of image quality used in optical design. Of these, theModulation Transfer Function (MTF) is particularly useful for opticaldesigns, simultaneously using two zones of optical power. The MTF is theefficiency of transferring the contrast of the original object to thecontrast of the image of the object on the human retina. The MTFefficiency (modulation) is plotted as a function of the spatialfrequency information in the image of the object. The spatial frequencycan be thought of as one divided by the size of features in the image.Thus, large spatial frequencies represent very fine features in theimage, and low spatial frequencies represent very large features in theimage. The image quality is maximized when the MTF values at selectedspatial frequencies have their highest values.

The assumptions are derived from the inlay's design requirement toprovide a good distance image from light rays passing through theperipheral region between the pupil diameter and the inlay's effect zone(r_(z)), and a good near image for light rays passing through thecentral effect zone. Thus, the ray-trace program is set with at leasttwo configurations. In the first, the object for the eye model is set toinfinity (e.g., looking at a distant object). In the secondconfiguration, the object is set at a near distance. The typicaldistance of near work and ophthalmic prescription is 40 cm, whichcorresponds to a spectacle ADD of 2.5 diopters.

For each configuration, the model eye's pupil size must be set. Of themany choices, two are the most logical. In the first, the pupil size isset the same for both configurations and goal of the optimization is tofind the elevation parameters which give equal distance and near imagequality. The second choice is to set separate pupil sizes for thedistance and near configurations. The near configuration pupil size isset to subject's pupil size in a well illuminated setting i.e., theperipheral distance zone is effectively zero. This condition providesthe maximal near distance capability. The distance configuration pupilsize is set to the subject's night-time or dim-light pupil size, wheredistance vision is maximized. For the examples provided herein, thelatter method was used, using different pupil sizes for the distance andnear configurations. Note that regardless of the method chosen, the samerange of ideal elevation profiles (e.g., Table 1) will be found.

The human pupil size varies for a given set of illumination conditions,with two important trends. As an individual ages, the nighttime pupilsize decreases. Additionally, when looking at a near object, the pupildiameter reduces by about 0.5 mm. Based on literature and clinicalexperience, the near configuration pupil in bright lighting isconsidered “small” if approximately 2.5 mm in diameter, “nominal” ifapproximately 3.0 mm, and “large” if approximately 3.5 mm in diameter.For the distance configuration, the nighttime pupil sizes vary greatly,and any loss of distance vision is compensated for by the fellow eye.Thus, one nighttime pupil size is sufficient for design purposes and adiameter of 5.0 mm is suggested by the literature/clinical experience.

The optimization tools of the ray-trace software program are nowutilized. The elevation parameters (hctr, r_(z), a6 and a8) are varieduntil the MTF of the near configuration is maximized whilesimultaneously maximizing the MTF of the distance configuration. Theideal design is clearly a function of the assumed pupil sizes. Inpractice, subject may be screened preoperatively, allowing the surgeonto select the inlay design most appropriate for the subject's pupil sizerange and desired visual outcome.

In this particular method of implanting an inlay, once the desiredanterior surface change has been determined, the inlay to be implantedis selected, taking into account and compensating for a biomechanicalresponse and an epithelial response due to the presence of the inlay.Exemplary biomechanical interactions which can be taken intoconsideration can be found in U.S. patent application Ser. No.11/738,349, filed Apr. 20, 2007, to which this application claimspriority and which is incorporated by reference herein.

Empirical data presented herein below provides details of some aspectsof a biomechanical response and an epithelial response due to thepresence of an intracorneal inlay.

Petroll et al. noted that intracorneal inlays induced epithelialthinning of the epithelium overlying the inlay. FIG. 5 illustrates across-section side view of inlay 500 positioned within the cornea stromalayer. Imaging a portion of the cornea with optical coherence tomography(OCT) has shown that after an inlay is positioned within the cornea, theepithelial layer attempts to reduce an induced change in shape in theanterior surface of the cornea. There has been a noticed epithelialthinning 502 radially above the inlay, and an epithelial thickening 504at locations slightly beyond the diameter of the inlay. The epitheliallayer remains unchanged in outer region 506. This epithelial remodelingappears to be a natural response by the epithelial layer to smooth out,or reduce, the induced increase in curvature of the anterior surface ofthe cornea. By thinning in region 502 and thickening in region 504, theepithelium remodels and attempts to return the anterior surface to itspre-operative shape. Epithelial remodeling in this context is theepithelial layer's way of attempting to reduce the change induced by theimplantation of a foreign object within the cornea. The thinning andthickening have each been observed to be about 10 microns.

This epithelial remodeling will adjust the shape of the anterior surfaceof the cornea after the inlay has been implanted. This will adjust therefractive effect of the inlay. In the examples described above,epithelial remodeling will attempt to reduce an induced steepening incurvature of the central effected zone by thinning a central region ofthe epithelium and thickening a peripheral portion of the epithelium.Understanding the epithelial remodeling is therefore important tounderstand how an inlay will ultimately change the shape of the anteriorsurface of the cornea. In some embodiments, therefore, selecting aninlay to be implanted within the cornea to be used for center nearvision comprises selecting an inlay that will compensate for epithelialremodeling and still cause the anterior surface of the cornea to adjustto the desired shape. Huang et al. describes the effects of epithelialremodeling as it relates to ablation of cornea tissue (i.e., removal oftissue). Huang, however, fails to address an epithelial remodeling afterthe addition of material to the cornea, such as an intracorneal inlay.An embodiment herein focuses on the epithelial remodeling after theaddition of material to the cornea.

FIG. 6 illustrates a cross-sectional side view of a portion of a corneabefore and after implantation of an intracorneal inlay 600. The changein the central region of Bowman's layer “DCenBow” is shown by thedifference in the two arrows. Similarly, the changes in a peripheralregion of Bowmans' layer “DPerBow”, the central anterior surface ofcornea “DCenCor”, and a peripheral region of the anterior surface ofcornea “DPerCorn” are represented.

FIG. 7 presents clinical data (e.g., distance and near visual acuity andthe refractive effect created by the inlay) and the change in anteriorcorneal surface elevation derived from pre-op and post-op wavefrontmeasurements of nine patients in whom a 1.5 mm diameter inlay with anaverage center thickness of about 32 microns (ranging from 30 microns to33 microns) was implanted. The “Postop ucnVA” column shows thepost-operative uncorrected near visual acuity. The second “PostuncNL”column shows the lines of uncorrected near visual acuity change(positive represents a gain while negative represents a loss). The“PostOp ucDVA” column shows the post-operative uncorrected distancevisual acuity. The “PostucDL” column shows the lines of uncorrecteddistance visual acuity change (positive represents a gain while negativerepresents a loss). The “InlayADDeff” column shows the refractive effectof the inlay calculated from clinical refraction data. The “InlayCen2.5mmSph” column shows the refractive effect of the inlay, centered on theinlay for a 2.5 mm diameter pupil, calculated from Tracey wavefrontdata. The “Diff Fit Ht” column shows the central anterior cornealelevation change (i.e., the difference between post-op and pre-op)calculated from Tracey wavefront data. The “Diff Eff Dia” column showsthe effect zone diameter. FIG. 8 charts the changes in elevation of theanterior surface of the cornea (i.e., the difference in elevationbetween pre-op and post-op) versus the radius of the anterior surface ofthe cornea for the nine patients in whom the 1.5 mm diameter inlay wasimplanted.

FIG. 9 presents clinical data the change in anterior corneal surfaceelevation derived from pre-op and post-op wavefront measurements ofseven patients in whom a 2.0 mm diameter inlay with an average centerthickness of about 32 microns (ranging from 31 microns to 33 microns)was implanted. The column headings are the same as those shown in FIG.8. FIG. 10 charts the changes in elevation of the anterior surface ofthe cornea (i.e., the difference in elevation between pre-op andpost-op) versus the radius of the anterior surface of the cornea for theseven patients in whom the 2.0 mm diameter inlay was implanted.

As shown in the data there is patient-to-patient variability withrespect to the epithelial remodeling of the cornea. The designs andmethods described herein, however, show effectiveness despite thisvariability.

A merely exemplary method for designing or selecting an implantablecornea device such as a small inlay to provide for central near visionand peripheral distance visions, which also compensates for epithelialremodeling or other physiological responses to the inlay will now begiven. One step in the method is determining a maximum effect zonediameter (d_(eff)) that is an acceptable tradeoff between the nearvision improvement and the loss of distance vision. Considerationsinclude the pupil size of the specific subject or a group ofcharacteristic subjects (e.g., subjects within a particular age range)while reading or viewing nearby objects, and the pupil size for distanceviewing, especially at night. Based on the analysis of pupil sizesrecorded in subjects with various intracorneal inlays, consideration ofthe distance and near visual acuities, review of literature on pupilsize changes, and supplemental theoretical ray-trace analysis oftheoretical eyes with the intracorneal inlay, in some embodiments thedesired effect zone diameter is between about 2.0 mm and about 4.0 mm.In an exemplary application, the inlay is placed in one eye to providenear vision while distance correction by other means is performed onboth the inlay eye and the fellow eye. In this example, both eyescontribute to distance vision, with the non-inlay eye providing thesharpest distance vision. The eye with the inlay provides near vision.

An additional step in the method is to determine the inlay diameter. Asshown above, the “effect” zone increases with inlay diameter. Based onempirical data discussed above in FIG. 7 regarding implanting an inlaywith a diameter of 1.5 mm, the inlay can be selected to have a diameterbetween about 1.5 mm and about 2.9 mm less than the diameter of thedesired effect zone diameter. Excluding the 3.0 mm effect zone diameterfrom patient 7, the inlay can be selected to have a diameter betweenabout 2.2 mm and 2.9 mm less than the diameter of the desired effectzone diameter. Based on the average effect zone diameter of 3.9 mm fromall nine patients, in some embodiments the inlay is selected to have adiameter of about 2.4 mm less than the effect zone diameter.

Based on empirical data discussed above in FIG. 9 regarding implantingan inlay with a diameter of 2.0 mm, the inlay can be selected to have adiameter between about 1.6 mm and about 2.4 mm less than the diameter ofthe desired effect zone diameter. In some embodiments the inlay can beselected to have a diameter between about 1.8 mm and about 2.4 mm lessthan the diameter of the desired effect zone diameter. Based on theaverage effect zone diameter of 4.0 mm from all seven patients, in someembodiments the inlay is selected to have a diameter of about 2.0 mmless than the effect zone diameter. In this manner an inlay diameter canbe selected which compensates for epithelial remodeling.

An additional step is to determine the inlay's posterior radius ofcurvature. The inlay is positioned on a lamellar bed, which is theanterior aspect of the cornea underneath the flap (in embodiments inwhich a flap is created). The posterior curvature of the inlay shouldmatch the curvature of the lamellar bed to prevent diffuse material fromfilling in gaps between the inlay and the lamellar bed, which can leadto optical opacities. For inlays which are “stiffer” (i.e., greatermodulus of elasticity) than the cornea, pre-operative estimates of thebed curvature are used to select the inlay with the appropriateposterior curvature. In the preferred embodiment, the inlay is moreflexible (i.e., modulus of elasticity less than or equal to about 1.0MPa) than the cornea (corneal modulus about 1.8 MPa), and the inlay willbend and conform to the bed curvature when placed under the flap.Analysis of the posterior shape of the implanted inlays by means ofOptical Coherence Topography suggests that bed radius of curvatureranges between 6 mm and 9 mm. To avoid any possibility of a gap beneaththe inlay, in some embodiments the posterior radius of curvature isabout 10 mm.

An additional optional step is to determine the inlay edge thickness. Afinite edge thickness 16 (see FIG. 1) creates a gap under the flap atthe peripheral edge of the inlay, potentially leading to biochemicalchanges resulting in opacities in the cornea. Thus, in some embodimentsthe edge thickness is minimized and preferably is less than about 20microns. In some embodiments the edge thickness is less than about 15microns.

An additional step is determining the inlay center thickness (see “T” inFIG. 1). Based on the clinical data above shown in FIG. 7 in which a 1.5mm diameter inlay is implanted (average center thickness of about 32microns), the inlay center thickness is selected to be between about 3.0and about 7 times the desired central anterior elevation change. Basedon the average of 6.6 microns in central anterior elevation change, inone particular embodiment the inlay center thickness is determined to beabout 5 times the desired central anterior elevation change. This datatherefore shows a factor of about 5 for the inlays with a diameter of1.5 mm.

Based on the clinical data above shown in FIG. 9 in which a 2.0 mmdiameter inlay is implanted (average center thickness of about 32microns), the inlay center thickness is selected to be between about 4.5and about 6.0 times the desired central anterior elevation change. Basedon the average of 6.2 microns in central anterior elevation change, inone particular embodiment the inlay center thickness is determined to beabout 5 times the desired central anterior elevation change. This datatherefore shows a factor of about 5 for the inlays with a diameter of2.0 mm.

An additional step is determining the inlay anterior radius ofcurvature. The inlay's anterior surface shape and curvature influencethe shape and curvature of the portion of the cornea's anterior surfaceabove the inlay and the outer effect zone. A range of anterior radii ofcurvatures, based on empirical evidence (some of which can be found inU.S. patent application Ser. No. 11/738,349, filed Apr. 20, 2007, (U.S.Patent Application No. US 2008/0262610 A1, which is incorporated hereinby reference) is between about 5.0 mm and about 10.0 mm. In someembodiments the selected anterior radius of curvature is between about 6mm and about 9 mm. In particular embodiments the anterior radius ofcurvature is about 7.7 mm or about 8.5 mm. While spherical anterior andposterior surfaces have been described herein, non-spherical surfacesmay be desirable. Such aspheric anterior inlay surfaces may be eitherflatter or steeper compared to a spherical surface.

An optional additional step is to determine an optional edge taper orbevel. Exemplary bevels are described in detail in U.S. patentapplication Ser. No. 11/106,983, filed Apr. 15, 2005 (Patent ApplicationPub. US 2005/0246016 A1), the disclosure of which is incorporated byreference herein. The shape of the bevel and the curvature of theanterior surface affect how fast the anterior surface outer effect zonereturns to the original anterior corneal surface and influences theanterior corneal surface's outer effect zone shape. The outer effectzone shape in turn determines the distribution of dioptic powers in theouter effect zone region and the retinal image quality for primarilyintermediate and near objects. The subtleties of the taper zone shapebecome most important when a sophisticated biomechanical model of theinlay and corneal interaction has been derived.

The above method is merely exemplary and not all of the steps need beincluded in selecting inlay parameters. For example, the inlay need nothave a bevel and therefore selecting a bevel length or shape need not beperformed when selecting an inlay profile to compensate for epithelialremodeling.

While portions of the disclosure above have highlighted selecting aninlay with specific features to compensate for an epithelial response,this disclose also includes methods of compensating for an epithelialresponse from a variety of other vision correcting intracornealprocedures. The discussion herein focuses on procedures that alter thestroma layer and for which the epithelial layer remodels to reduce theeffect of the intracorneal procedure. One category of vision correctionprocedures that alter the stroma are procedures which remodel the corneatissue. For example, corneal ablation procedures such as LASIK areincluded in this category. Remodeling the corneal tissue can be donewith lasers, such as ultraviolet and shorter wavelength lasers. Theselasers are commonly known as excimer lasers which are powerful sourcesof pulsed ultraviolet radiation. The active medium of these lasers arecomposed of the noble gases such as argon, krypton and xenon, as well asthe halogen gases such as fluorine and chlorine. Under electricaldischarge, these gases react to build excimer. The stimulated emissionof the excimer produces photons in the ultraviolet region.

Procedures that alter the stroma layer also include procedures thatweaken corneal tissue without ablating the tissue. 20/10 Perfect Visionhas developed the intraCOR® treatment, for example, an intrastromalcorrection of presbyopia using a femtosecond laser. Procedures thatintroduce a foreign body or matter into the cornea, such as an inlay,are also included in this category. It is also contemplated that aflowable media, such as a fluid or uncured polymeric composition, couldbe positioned within the cornea as well to be used to correct vision.

These additional cornea procedures will provoke an epithelial responsewhich in some embodiments is compensated for when performing theprocedures. For example, corneal ablation procedures remove cornealtissue which changes the curvature of the anterior surface of thecornea. The epithelial layer then remodels to try and reduce the shapechange. Performing the procedure to compensate for this epithelialremodeling will therefore allow the procedure to produce the desiredchange to the cornea.

FIGS. 11-13 illustrate an additional exemplary method of correctingvision that uses a laser to remodel cornea tissue to induce a shapechange in the anterior surface of the cornea. Just as in the embodimentsabove, FIGS. 11-13 illustrate a method of correcting for presbyopia thattakes epithelial remodeling into consideration. In the method of FIGS.11-13, a lenticule is created in the stroma and then removed to induce ashape change to the anterior surface of the cornea. General methods oflenticule creation and extraction, any of which can be used in any ofthe methods herein, can be found in the following U.S. Publications, thecomplete disclosures of which are incorporated by reference herein:2010/0331831 to Bischoff et al., published on December 2010;2014/0128855 to Wottke et al., published May 8, 2014; and 2014/0288540to Bischoff et al., published Sep. 25, 2014. Lenticule extractionmethods therein are commonly referred to as the “FLEx” and “SMILE”procedures. The procedures use a short-pulse laser, such as afemtosecond laser, to create an incision geometry in the cornea,separating a cornea volume (so-called “lenticule”) in the cornea. Ratherthan ablating corneal tissue, both methods rely on lenticule creationand extraction. An exemplary advantage of these methods is that thequality of the incision is further improved by using a short pulselaser, such as a femtosecond laser. Additionally, only a singletreatment device is needed; an excimer laser is not needed.

In the FLEx procedures, the lenticule is removed manually by the surgeonafter the flap covering the lenticule has been folded back. A refinementof the FLEx method is referred to as the “SMILE” (Small IncisionLenticule Extraction) method in which no flap is created but rather onlya small opening incision that serves to access the lenticule locatedbeneath the so-called cap. The separated lenticule is removed throughthis small opening incision, as a result of which the biomechanicalintegrity of the anterior cornea is less affected than in a LASIK, FLExor PRK (photorefractive keratectomy) procedure. Moreover, in thismanner, fewer superficial nerve fibers in the cornea are cut and thishas been proven to be advantageous when it comes to the restoration ofthe original sensitivity of the surface of the cornea. As a result, thesymptom of dry eyes that often has to be treated after a LASIK procedureis often less severe and less protracted. Other complications afterLASIK, which usually have to do with the flap (e.g., folds, epithelialingrowth in the flap bed) occur less often in procedures without a flap.

The methods of lenticule creation and extraction described in the threepatent application publications above are expressly incorporated byreference herein. In some of the methods described, lenticule creationand extraction can be used to treat myopia by removing the lenticule,which flattens the anterior surface of the cornea. For example, U.S.Publication 2014/0128855, in FIGS. 6A-7B, illustrates two exemplarymethods of lenticule creation and extraction.

FIGS. 11-13 illustrate a method of lenticular extraction that correctsfor presbyopia as well as treating myopia, although the methods hereincan be used for other vision correction procedures.

FIG. 11 illustrates a portion of cornea 600 before the procedure hasbegun. FIG. 12 illustrates cornea 600 after lenticule 601 (shown inhashed lines) has been created with a femtosecond laser. Creatinglenticule 601 includes creating anterior lenticule incision 602,posterior lenticule incision 603 (with a solid line), lenticule edgeincision 604, and opening incision 605. Posterior lenticule incision 603includes a peripheral region 606 and a central region 607. As shown,central region 607 of the posterior lenticule incision has an increasedcurvature relative to peripheral region 606. Central region 607 ofposterior lenticule incision 603 increases the curvature of a centralportion of the anterior surface of the cornea relative to a peripheralportion of the anterior surface of the cornea to correct for presbyopia,as is described herein. In this exemplary embodiment, removal of thelenticule also causes a flattening of the anterior surface of the corneaperipheral to the steepened central region, the flattened regioncorrecting for myopia, as is shown in FIG. 13.

In this embodiment shown in FIG. 12, lenticule 601 has a meniscus shape,which corrects for myopia by flattening the anterior surface of thecornea when the lenticule is removed. In other embodiments clearlycontemplated herein, however, the lenticule can be created with a shapethat is configured to correct other refractive errors, such ashyperopia. For example, other lenticule shapes can be created that, whenremoved, remove more corneal tissue in the peripheral region of thepupil, causing an increase the curvature of the anterior surface of thecornea and correcting for hyperopia. The methods herein include anysuitable lenticule shape, as long as it still causes an increase incurvature in a central region of the anterior surface of the cornea toprovide near vision as described herein.

Extension 608 (shown in dashed lines) illustrates an imaginary extensionsurface of peripheral region 603 extending across central region 607.Extension 608 can be drawn for purposes of measuring central thickness609 of central region 607. In this embodiment central thickness 609 isabout 50 microns or less, and is measured as the greatest lineardistance from extension 608 to posterior lenticule incision 603 incentral region 607. Similar extension surfaces can be drawn regardlessof the shape of peripheral region 603. For example, extension 608 couldbe a flat surface if peripheral region 603 is flat. In this embodimentcentral region 607 has an outer diameter 610 between 1 mm and 4 mm. Insome embodiments lenticule 601 has an outermost diameter between 1 mmand 8 mm.

The exemplary method also includes removing the lenticule from thestroma, which causes an increase in the curvature of a central portionof the anterior surface of the cornea for near vision, wherein theincrease in curvature of the central portion of the anterior surface ofthe cornea has a central elevation change. FIG. 13 illustrates cornea600 after lenticule 601 has been removed through incision opening 605.Removal of lenticule 601 causes flattening of the cornea in peripheralregion 612 to correct for myopia (due to the shape of the lenticule),but the central bump 607 created in the posterior lenticule incision 603causes a region of increased relative curvature 611 in the anteriorsurface of the cornea, which provides near vision and corrects forpresbyopia. Central elevation change 613 in the central region due tocentral bump region 607 is also illustrated, which as is described inmore detail above. The posterior lenticule incision is illustrated inthe cornea to illustrate the location of the incision after lenticule601 has been removed.

In other embodiments an emmetrope can be treated by creating a lenticulethat is equally thick across its width (optionally with a taper at theperiphery), with the lenticule including a central bump as describedherein.

As is described in more detail above, the methods of lenticuleextraction that correct for presbyopia also take into consideration, andplan for, epithelial remodeling. The entire disclosure above related totaking epithelial remodeling therefore applies to the methods oflenticule extraction herein. For example, in this embodiment, centralthickness 609 is about 50 microns or less measured from extension 608and is 3 to 7 times the central elevation change 613. All of the otherfactors for procedure planning that are described above, are, however,applicable to central region 607.

In the embodiment in FIGS. 11-13 central region 607 is shown anddescribed as being created in the posterior lenticule incision 603. Inany of the methods herein, however, central bump region 607 canalternatively be created in a central region of the anterior lenticuleincision 602. In these methods the thickness of the central bump regionis measured from an imaginary extension of the anterior lenticuleincision. In any of the methods herein, alternatively still, both theanterior lenticule incision and the posterior lenticule incision canhave a central bump region thereon, with the part-bumps on each of theanterior lenticule incision and the posterior lenticule incisiontogether being considered the central bump region. In any of thesemethods, the central bump region causes an increase in curvature in acentral region of the anterior surface of the cornea to correct for nearvision.

What is claimed is:
 1. A method of correcting vision for presbyopia,comprising: remodeling the stroma with a laser to create an intracornealshape, wherein the corneal shape includes a central region with athickness that is about 50 microns or less measured from an extension ofa shape of a peripheral region of the corneal shape, wherein remodelinga portion of the stroma increases a curvature of a central portion ofthe anterior surface of the cornea with a central elevation change fornear vision while allowing distance vision in a region peripheral to thecentral portion; wherein the corneal shape compensates for epithelialremodeling of the epithelial layer of the cornea in response toremodeling the stroma, and wherein the central region with a thicknessthat is about 50 microns or less measured from an extension of a shapeof the peripheral region of the corneal ablation shape is 3 to 7 timesthe central elevation change.
 2. The method of claim 1 wherein theremodeling step is performed without ablating the stroma.
 3. The methodof claim 1 wherein the remodeling step creates a corneal lenticule, andthe intracorneal shape is defined by a posterior lenticule incision. 4.A method of correcting vision for presbyopia, comprising: creating alenticule in a stroma, wherein creating the lenticule includes creatingan anterior lenticule incision and a posterior lenticule incision with afemtosecond laser, wherein one of the posterior lenticule incision andthe anterior lenticule incision has a central region and a peripheralregion, the central region having increased curvature relative to theperipheral region, and a central thickness that is about 50 microns orless measured from an extension of the peripheral region, the centralregion having an outer diameter between 1 mm and 4 mm; and removing thelenticule from the stroma, wherein removing the lenticule increases thecurvature of a central portion of the anterior surface of the corneawith a central elevation change for near vision; wherein one of theposterior lenticule incision and anterior lenticule incision compensatesfor epithelial remodeling of the epithelial layer of the cornea inresponse to cutting and removing the lenticule in the stroma, andwherein the central thickness that is about 50 microns or less measuredfrom an extension of the peripheral region is 3 to 7 times the centralelevation change.
 5. The method of claim 4 wherein creating the anteriorlenticule incision comprises creating the anterior lenticule incisionbetween 5 microns and 250 microns deep in the stroma.
 6. The method ofclaim 4 wherein removing the lenticule comprises creating a cornealflap.
 7. The method of claim 4 wherein the method of correcting visiondoes not include creating a corneal flap.
 8. A method of correctingvision for presbyopia, comprising: creating a lenticule in a stroma,wherein creating the lenticule includes creating an anterior lenticuleincision and a posterior lenticule incision with a femtosecond laser,wherein the posterior lenticule incision has a posterior peripheralregion and a posterior central region, and the anterior lenticuleincision has an anterior central region and an anterior peripheralregion, the anterior and posterior central regions having increasedcurvature relative to the anterior and posterior peripheral regions, theanterior and posterior central regions having a combined thickness thatis about 50 microns or less measured from extension of the peripheralregions, the anterior and posterior central regions having an outerdiameter between 1 mm and 4 mm; and removing the lenticule from thestroma, wherein removing the lenticule increases the curvature of acentral portion of the anterior surface of the cornea with a centralelevation change for near vision; wherein the posterior lenticuleincision and the anterior lenticule incision compensate for epithelialremodeling of the epithelial layer of the cornea in response to cuttingand removing the lenticule in the stroma, and wherein the combinedcentral thickness that is about 50 microns or less measured fromextensions of the peripheral regions is 3 to 7 times the centralelevation change.